SVV-001 With Nivolumab and Ipilimumab in Patients With Poorly Differentiated Neuroendocrine Carcinomas (NEC) or Well-Differentiated High-Grade Neuroendocrine Tumors (NET)

NCT06889493 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20231325
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine:

1. 1.The highest dose of the trial intervention that targets neuroendocrine tumors and is tolerated by patients.
2. 2.The highest frequency of dosing of the trial intervention that targets neuroendocrine tumors and is tolerated by patients.
3. 3.The highest dose and frequency of dosing of the trial intervention that targets neuroendocrine tumors with at least the same degree of effectiveness and tolerability as currently available (standard of care) treatments for patients with neuroendocrine tumors.

Conditions

Neuroendocrine Carcinoma; Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose

  MTD is defined as the highest dose of SVV-001 evaluated for which estimated toxicity rate is the closest to the target toxicity rate as assessed by treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The MTD will be established as the recommended phase 2 dose (RP2D).

  Up to 12 months

• Number of Participants Experiencing Dose Limiting Toxicities (DLTs): Part 1 Only

  The number of participants experiencing dose limiting toxicities (DLTs) in Part 1 will be reported. DLTs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 12 months

• Number of Participants Experiencing Treatment-Related Serious Adverse Events (SAEs)

  The number of participants experiencing treatment-related serious adverse events (SAEs) after starting study therapy will be reported. SAEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 12 months

• Number of Participants Experiencing Treatment-Related Adverse Events (AEs)

  The number of participants experiencing treatment-related adverse events after starting study therapy will be reported. AEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 12 months

Secondary Outcomes (7)

• Progression-Free Survival (PFS) Measured by RECIST

  Up to 12 months

• Progression-Free Survival (PFS) Measured by iRECIST

  Up to 12 months

• Overall Response Rate (ORR) Measured by RECIST

  Up to 12 months

• Overall Response Rate (ORR) Measured by iRECIST

  Up to 12 months

• Duration of Response (DOR)

  Up to 2 years

Study Arms (3)

SVV-001 Single Dose Treatment Group

EXPERIMENTAL

Participants in this group will receive a single dose of SVV-001 on Day 1, in combination with Nivolumab and Ipilimumab therapy. Total participation duration is up to 2 years.

Biological: Seneca Valley Virus-001 (SVV-001); Drug: Nivolumab; Drug: Ipilimumab

SVV-001 Multi-Dose Treatment Group

EXPERIMENTAL

Participants in this group will receive multiple doses of SVV-001, beginning on Day 1, in combination with Nivolumab and Ipilimumab therapy. Total participation duration is up to 2 years.

Biological: Seneca Valley Virus-001 (SVV-001); Drug: Nivolumab; Drug: Ipilimumab

SVV-001 RP2D Treatment Group

EXPERIMENTAL

Participants is this group will receive the recommended phase 2 dose and frequency of SVV-001 in combination with Nivolumab and Ipilimumab therapy. Total participation duration is up to 2 years.

Biological: Seneca Valley Virus-001 (SVV-001); Drug: Nivolumab; Drug: Ipilimumab

Interventions

Seneca Valley Virus-001 (SVV-001) BIOLOGICAL

SVV-001 will be administered intratumorally as a single dose on Day 1; or as multiple doses on Days 1, 15, 29, 43, 57, and 71. The virus dose levels per SVV-001 treatment are as follows: * 2.2 × 10\^8 Viral Genomes (VG) (starting dose) * 2.2 × 10\^9 VG * 2.2 × 10\^10 VG

SVV-001 Multi-Dose Treatment Group; SVV-001 RP2D Treatment Group; SVV-001 Single Dose Treatment Group

Nivolumab DRUG

Nivolumab will be administered via intravenous (IV) injection at a dose of 240 mg, once every two weeks starting on Day 15 until Day 85 during SVV-001 therapy. Nivolumab will be administered once every four weeks during the maintenance period for up to 2 years.

SVV-001 Multi-Dose Treatment Group; SVV-001 RP2D Treatment Group; SVV-001 Single Dose Treatment Group

Ipilimumab DRUG

Ipilimumab will be administered via intravenous (IV) injection at a dose of 1 mg/kg, once every six weeks starting on Day 15 until Day 85 during SVV-001 therapy. Participants will continue on 1 mg/kg ipilimumab IV every 6 weeks for two additional doses or unacceptable toxicity and/or participant withdrawal.

SVV-001 Multi-Dose Treatment Group; SVV-001 RP2D Treatment Group; SVV-001 Single Dose Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 18 years of age or older at the time of consent.
• Life expectancy of 6 months or greater as assessed by the treating oncologist.
• Have advanced metastatic disease that has progressed on at least one line of available therapy.
• Histologically or cytologically confirmed diagnosis of Grade 3 well-differentiated neuroendocrine tumor (NET) or poorly differentiated neuroendocrine carcinoma (NEC; large-cell neuroendocrine carcinoma, small-cell carcinoma, mixed neuroendocrine non neuroendocrine carcinoma). Note: if an archival tissue sample collected ≤ 2 years from enrollment is unavailable at Screening for diagnostic confirmation, at the Principal Investigator's (PI's) discretion, a screening biopsy will be ordered.
• Parts 1B and 2 only: Measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or immune-related Response Evaluation Criteria in Solid Tumors (iRECIST). At least one lesion must be suitable for multiple injections (up to 6 injections every 2 weeks) with SVV-001. Lesions for injection must be ≥10 mm in longest diameter and deemed safe and suitable for injection by the Investigator.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Recovered to Grade 1 or baseline from any clinically significant toxicity associated with prior treatments (excluding alopecia) prior to initiation of investigational medicinal product (IMP) administration.
• Adequate hematological, renal, and liver function defined as follows:
• a. Hepatic:
• i. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) (≤5 × ULN if liver metastases are present)
• ii. Serum bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome or hemolysis)
• b. Renal:
• i. Creatinine clearance ≥50 mL/minute using Cockcroft Gault equation
• c. Hematologic:
• i. Absolute neutrophil count ≥1500 cells/µL

You may not qualify if:

• Any active second malignancy within the 2 years prior to the screening visit, unless the patient has undergone curative surgery for the tumors such as in situ cervical cancer or squamous cell cancer of the skin.
• Has had cytotoxic chemotherapy or radiation therapy within 3 weeks; and less than 5 half-lives or 6 weeks, whichever is shorter, from prior biologic therapies, prior to the first dose of SVV-001.
• Has undergone a major surgical procedure (as defined by the Investigator) or significant traumatic injury within 28 days prior to the first dose of SVV-001.
• Has any physical abnormality of the tissue/organ to be biopsied that would put the patient at increased risk of bleeding secondary to the injection and/or biopsy.
• Has received a live-virus immunization within 30 days prior to the screening visit or anticipates receiving a live virus immunization during the trial or within 30 days of the last treatment with IMP.
• Presence of primary immunodeficiency or receiving systemic steroids of \>10 mg/day prednisone or equivalent or other immunosuppressive agents within 14 days prior to the first dose of SVV-001.
• Any active infection, including known infection with human immunodeficiency virus (HIV), active hepatitis, or seropositive for hepatis B immunoglobulin (Ig) M core antibody or hepatitis C ribonucleic acid (RNA) at the screening visit.
• Patients with a history of solid-organ or bone marrow transplant.
• Known hypersensitivity to ipilimumab or nivolumab or their excipients
• Has known untreated central nervous system metastases. Patients with treated brain metastases are eligible as long as they are stable and there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging (MRI) or computed tomography (CT)) during the screening period.
• Any clinically significant (i.e., active) cardiovascular disease, including cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Patients with an ejection fraction (EF) \< 50 on a 2D echocardiogram (ECHO).
• Patients whose baseline pulse oximetry (saturation of peripheral oxygen (SpO2)) is \< 92% on Room air.
• Any chronic illness, psychiatric condition, or social situation that is life threatening or, in the opinion of the Investigator, renders the patient unsuitable for participation in a clinical trial due to possible noncompliance or would place the patient at an unacceptable risk and/or have the potential to affect interpretation of the results of the trial.
• Female participants who are breastfeeding and/or who have a positive pregnancy test result prior to receiving any treatment with IMP.

Sponsors & Collaborators

• Peter Hosein, MD: lead
• Seneca Therapeutics: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Neuroendocrine; Neuroendocrine Tumors

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Peter Hosein, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Hosein, MD

CONTACT

+1 (305) 2438173; nxr518@med.miami.edu

Nailet Real Bestard, MS

CONTACT

+1 (305) 2438173; nxr518@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Clinical

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: March 21, 2025
• Study Start: May 19, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)